1. Field of the Invention
The present invention relates to fluid connectors that are suitable for use in apparatus for delivering fluids, such as drugs, to different parts of the human or animal body. In particular, the invention relates to male and female connector portions suitable for use in a modular drug distribution apparatus for delivering drugs to the brain.
2. Description of Related Art
The drug treatment of a number of neuro-degenerative disorders, hereditary neurological disorders, brain tumours and other diseases of the nervous system are compromised by the presence of the blood brain barrier which prevents the transfer of drugs from the vascular system or cerebrospinal fluid into the brain substance. Examples of drugs which do not adequately cross the blood brain barrier include protein molecules such as neurotrophins, monoclonal antibodies, viral particles for delivery of gene therapy, as well as a number of cytotoxic drugs for the treatment of tumours.
Such drugs may be delivered to the brain by direct infusion into the parenchyma via an indwelling catheter. Upon exiting the catheter the drugs will be dispersed through the brain substance down a concentration gradient (i.e. by diffusion) and/or down a pressure gradient by the process of convection. Large molecules diffuse poorly and so drug delivery into the brain may be best modulated by controlling the rate of drug infusion and thus the degree to which the drug is convected. Convected infusate will carry large molecules such as proteins and viral particles by bulk flow through the interstitial spaces to fill the selected brain volume.
For a number of conditions it is desirable to maximise the volume of drug delivery from a single catheter, as well as to achieve a homogenous concentration of drug throughout the treatment volume. The process by which this is achieved is termed convection enhanced delivery. This may be accomplished, by inserting a catheter with a small external diameter. For example, a catheter of the type described in WO2003/077758 could be used. The drug can then be infused at a flow rate which will preferentially drive the infusate into the interstitial fluid at a maximum tolerated rate that will not cause tissue damage, but also at a rate which will prevent significant reflux along the catheter tissue interface.
For a number of neurological conditions it is desirable to deliver drugs to large volumes of the central nervous system and these would include the treatment of primary or secondary brain tumours, hereditary disorders and conditions such as multiple sclerosis, where any part of the central nervous system may be affected. In these circumstances, it is often desirable to implant multiple catheters into the central nervous system in order to fill the desired volume of tissue with drug. In other conditions it may be desirable to confine a drug to a particular tissue volume so as to minimise its side effects; for example the delivery of GDNF to the striatum to promote its reinnervation with dopaminergic neurons. In these circumstances the desired treatment volume may be filled with a single catheter and the flow rate adjusted to fill the desired volume only.
A variety of implantable drug delivery systems are known and typically comprise a drug pump assembly that can be implanted into the abdomen and one or more flexible catheters that route drug from the pump to the required anatomical site or sites. An example of such an implantable pump is described in US2003/0216714.
For some applications, however, it is not desirable to implant a pump for drug delivery because infrequent repeated treatments are required, such as every few months, which would negate the necessity for long-term implantation of a pump. Additionally for treatments requiring drug delivery to a substantial portion of the central nervous system large volumes of infusate may be required, for example in excess of 50 ml, which would require an excessively large pump reservoir to be implanted which would be inappropriate for infrequent use. Furthermore, some drugs may be unstable when stored at body temperature thus preventing the long term storage of such drugs within implanted reservoirs.
In order to be able to deliver drugs intermittently to the brain using an external pump assembly, the clinician is faced with several problems. The most significant problem is the risk of infection at the site where the tubing connecting the intraparenchymal catheter to the pump exits the skin. Although it is known that tubing for drug delivery into the venous system can be implanted for several months and remain substantially infection free with meticulous aseptic technique, an example of which is the Hickman line, this solution would not be suitable for intermittent drug delivery to the brain because the consequences of infection would be far greater and the period over which intermittent therapy may be given could extend over several years.
An alternative drug delivery solution may be to pass a needle through the skin to a subcutaneous drug infusion port, however, although the skin could be cleaned it cannot be made sterile and there remains a not insignificant risk of the needle carrying bacteria into the subcutaneous infusion port. If the infusion period is continued over many hours or a few days then the risk of infection along the needle track significantly increases. A sharp needle can also carry with it skin debris and this may be carried into the brain, or alternatively block the very fine tubing used for convection enhanced delivery. Furthermore, infusion pressures for convection enhanced delivery may be relatively high because of the very fine bore catheter tubing and extension tubing required. Retaining a transcutaneous needle in an infusion port would in these circumstances also be a concern. Additionally where drug delivery is required to multiple sites within the central nervous system, for example six or more, these problems are similarly multiplied.